Article
Hematology
Nicola Polverelli, Elena M. Elli, Elisabetta Abruzzese, Giuseppe A. Palumbo, Giulia Benevolo, Mario Tiribelli, Massimiliano Bonifacio, Alessia Tieghi, Giovanni Caocci, Mariella D'Adda, Micaela Bergamaschi, Gianni Binotto, Florian H. Heidel, Francesco Cavazzini, Monica Crugnola, Novella Pugliese, Costanza Bosi, Alessandro Isidori, Daniela Bartoletti, Giuseppe Auteri, Roberto Latagliata, Lisa Gandolfi, Bruno Martino, Luigi Scaffidi, Daniele Cattaneo, Fabio D'Amore, Malgorzata M. Trawinska, Rossella Stella, Uros Markovic, Lucia Catani, Fabrizio Pane, Antonio Cuneo, Mauro Krampera, Gianpietro Semenzato, Roberto M. Lemoli, Nicola Vianelli, Massimo Breccia, Domenico Russo, Michele Cavo, Alessandra Iurlo, Francesca Palandri
Summary: RUX treatment has been associated with a higher incidence of SPMs, with NMSCs being the most common. Risk factors for SPMs include male sex and thrombocytosis at RUX start. For SPMs excluding NMSCs, male sex, thrombocytosis, and previous arterial thromboses are considered high-risk factors.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Dermatology
Xiaonan Chen, Dong Zhang, Teng Wang, Weiyuan Ma
Summary: This article reports a case of Mycobacterium marinum skin infection in a female patient with chronic idiopathic myelofibrosis during treatment with ruxolitinib. The patient did not have any history of being punctured or scratched by fish scales or spines, but presented with multiple infiltrative erythemas and subcutaneous nodules in the thumb and forearm. The diagnosis was confirmed by NGS sequencing and the patient was cured after 10 months of treatment with moxifloxacin and clarithromycin.
CLINICAL COSMETIC AND INVESTIGATIONAL DERMATOLOGY
(2023)
Article
Oncology
Ruben A. Mesa, Stacie Hudgens, Lysbeth Floden, Claire N. Harrison, Jeanne Palmer, Vikas Gupta, Donal P. McLornan, Mary F. McMullin, Jean-Jaques Kiladjian, Lynda Foltz, Uwe Platzbecker, M. Laura Fox, Adam J. Mead, David M. Ross, Stephen T. Oh, Andrew Perkins, Michael F. Leahy, Samineh Deheshi, Rafe Donahue, Barbara J. Klencke, Srdan Verstovsek
Summary: This study evaluated the longitudinal change in total symptom score (TSS) and individual symptom scores in MF patients receiving therapy, and found that momelotinib provided clinically relevant symptom benefits compared to control group.
Article
Hematology
James R. R. Berenson, Daisy Martinez, Tahmineh Safaie, Ralph Boccia, Honghao Yang, Mehdi Moezi, Stephen Lim, Gary Schwartz, Shahrooz Eshaghian, Regina Swift, Benjamin M. M. Eades, Sean Bujarski, Bernard Regidor, Clara Kim, Susanna Kim, Robert Vescio
Summary: This study evaluated the efficacy of combination therapy with ruxolitinib and methylprednisolone for multiple myeloma patients. The results showed that this treatment regimen demonstrated significant clinical activity among heavily-treated patients and achieved responses in patients with high-risk cytogenetics.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Sangeetha Venugopal, John Mascarenhas
Summary: Myelofibrosis (MF) can lead to splenomegaly and thrombocytopenia. Currently approved JAK1/2 inhibitors have not been evaluated in patients with platelets <= 50 x 109/L. Pacritinib (PAC), a selective JAK2 inhibitor, has shown efficacy in MF patients, especially in splenic response and symptom improvement.
Article
Oncology
Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Naval G. Daver, Koji Sasaki, Helen T. Chifotides, Lingsha Zhou, Hagop M. Kantarjian, Zeev Estrov, Srdan Verstovsek
Summary: This retrospective study evaluated the impact of different therapies on the survival of patients with myelofibrosis. The results showed that treatment with the JAK inhibitor ruxolitinib improved patient outcomes. Approximately 61% of patients initiated MF-directed therapy, with ruxolitinib being the most common choice. About 32% of patients required second-line therapy.
Article
Immunology
Vincent C. Marconi, Carlee Moser, Christina Gavegnano, Steven G. Deeks, Michael M. Lederman, Edgar T. Overton, Athe Tsibris, Peter W. Hunt, Amy Kantor, Rafick-Pierre Sekaly, Randall Tressler, Charles Flexner, Selwyn J. Hurwitz, Daniela Moisi, Brian Clagett, William R. Hardin, Carlos Del Rio, Raymond F. Schinazi, Jeffrey J. Lennox
Summary: This study confirms the safety and efficacy of Ruxolitinib for HIV-infected individuals on ART. While there was no significant reduction in plasma IL-6 levels, Ruxolitinib significantly decreased markers of immune activation and cell survival.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Hematology
Aniket Bankar, Shabbir Alibhai, Elliot Smith, Dongyang Yang, Sarah Malik, Verna Cheung, Nancy Siddiq, Jaime Claudio, Andrea Arruda, Hubert Tsui, Jose-Mario Capo-Chichi, James A. Kennedy, Caroline McNamara, Hassan Sibai, Dawn Maze, Wei Xu, Vikas Gupta
Summary: Frailty is associated with shorter overall survival and increased JAK inhibitor therapy failure in patients with myelofibrosis, suggesting that higher frailty scores may be a more superior indicator of fitness compared to age, comorbidities, and performance status.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Oncology
Helen T. Chifotides, Prithviraj Bose, Srdan Verstovsek
Summary: Momelotinib has shown consistent benefits in treating anemia in myelofibrosis patients by inhibiting the BMP6/ACVR1/SMAD and IL-6/JAK/STAT3 pathways, resulting in improved iron and hemoglobin levels, as well as restored erythropoiesis. Clinical data from phase 2 and phase 3 trials demonstrate high rates of sustained transfusion-independence with Momelotinib compared to other treatments.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Hematology
John Mascarenhas
Summary: Myelofibrosis (MF) is a rare myeloproliferative neoplasm characterized by a complex symptom profile, cytopenias, splenomegaly, and potential for leukemic progression. Pacritinib, a potent Janus kinase (JAK) 2/interleukin-1 receptor-associated kinase 1 (IRAK1) inhibitor, has demonstrated significant reduction in splenomegaly, improved symptom control, and a manageable safety profile in patients with MF regardless of the severity of thrombocytopenia. Pacritinib offers MF patients with severe thrombocytopenia a new treatment option.
EXPERT REVIEW OF HEMATOLOGY
(2022)
Article
Hematology
Haris Ali, Ni-Chun Tsai, Timothy Synold, Sally Mokhtari, Weimin Tsia, Joycelynne Palmer, Tracey Stiller, Monzr Al Malki, Ibrahim Aldoss, Amandeep Salhotra, Syed Rahmanuddin, Vinod Pullarkat, Ji-Lian Cai, Anthony Stein, Stephen J. Forman, Guido Marcucci, Matthew Mei, David S. Snyder, Ryotaro Nakamura
Summary: This study reports the safety and feasibility of peritransplantation ruxolitinib for myelofibrosis treatment. The results show that this treatment is safe and well tolerated at a specific dose, and has promising early efficacy in high-risk older patients with myelofibrosis.
Review
Oncology
Srdan Verstovsek, Chih-Cheng Chen, Miklos Egyed, Martin Ellis, Laura Fox, Yeow T. Goh, Vikas Gupta, Claire Harrison, Jean-Jacques Kiladjian, Mihaela C. Lazaroiu, Adam Mead, Donal McLornan, Mary F. McMullin, Stephen T. Oh, Andrew Perkins, Uwe Platzbecker, Christof Scheid, Alessandro Vannucchi, Sung-Soo Yoon, Mark M. Kowalski, Ruben A. Mesa
Summary: Key features of myelofibrosis (MF) include low blood cell counts, constitutional symptoms and splenomegaly. Anemia and transfusion dependency are important negative prognostic factors. Momelotinib (MMB) is a unique JAK inhibitor that aims to improve MF symptoms and spleen size while also enhancing hemoglobin levels.
Article
Oncology
Naseema Gangat, Kebede H. Begna, Aref Al-Kali, William Hogan, Mark Litzow, Animesh Pardanani, Ayalew Tefferi
Summary: This retrospective study found that different JAK2 inhibitors had varying effects on spleen and transfusion-dependent anemia in patients with high/intermediate risk myelofibrosis. Age, genetic mutations, and treatment responses were all associated with overall survival. The study also confirmed the positive impact of treatment response on short-term survival and the long-term survival benefit of allogeneic stem cell transplants.
BLOOD CANCER JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Dong-Hua Yang, Qisi Lu, Zhaohui Zhu, Guanghao Huang, Katherine Young
Summary: Myelofibrosis is a progressive cancer that disrupts the production of healthy blood cells, leading to bone marrow failure. Patients with severe thrombocytopenia have increased disease burden and limited treatment options. Pacritinib, a new oral kinase inhibitor, targets specific enzymes and is indicated for the treatment of myelofibrosis patients with platelet count below a certain level.
Article
Chemistry, Medicinal
Jigar Desai, Bhaumin Patel, Archana Gite, Nandini Panchal, Sanjay Gite, Anil Argade, Jeevan Kumar, S. Sachchidanand, Debdutta Bandyopadhyay, Krishnarup Ghoshdastidar, Hoshang Patel, Abhijit Chatterjee, Jogeshwar Mahapatra, Manoranjan Sharma, Poonam Giri, Sanjay Kumar, Mukul Jain, Rajiv Sharma, Ranjit Desai
Summary: This study reports the design, optimization, synthesis, and biological evaluation of pyrimidine-based JAK inhibitors to obtain pan-JAK inhibitors. Compound 32 was discovered to potently inhibit JAK1, JAK2, and JAK3 and exhibited superior anti-inflammatory efficacy with favorable pharmacokinetic properties compared to momelotinib.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Hematology
Srdan Verstovsek, Naveen Pemmaraju, Nancy L. Reaven, Susan E. Funk, Tracy Woody, Frank Valone, Suneel Gupta
Summary: Polycythemia vera (PV), a type of myeloproliferative neoplasm, has an increased risk of thrombotic events (TE) and mortality. Treatment interventions, such as phlebotomy and cytoreductive medications, aim to maintain hematocrit levels below 45% for better outcomes. A retrospective observational study including 28,306 PV patients found that a majority of both high- and low-risk patients initiated treatment with phlebotomy monotherapy, but hematocrit control was suboptimal in both risk groups. Around 16% of individuals experienced at least 1 TE after treatment initiation, suggesting that current PV treatments may not be fully utilized.
ANNALS OF HEMATOLOGY
(2023)
Review
Oncology
Helen T. Chifotides, Lucia Masarova, Srdan Verstovsek
Summary: The development of MF therapeutics has achieved remarkable progress, with JAK2 inhibitors playing a transformative role in MPN treatment. In addition to these inhibitors, there are numerous novel monotherapies and rational combinations being developed to address different aspects of the disease. These advancements have the potential to improve patient outcomes and lead to a golden era in MF treatment.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Review
Hematology
Nicola Polverelli, Juan Carlos Hernandez-Boluda, Tomasz Czerw, Tiziano Barbui, Mariella D'Adda, Hans Joachim Deeg, Markus Ditschkowski, Claire Harrison, Nicolaus Martin Kroger, Ruben Mesa, Francesco Passamonti, Francesca Palandri, Naveen Pemmaraju, Uday Popat, Damiano Rondelli, Alessandro Maria Vannucchi, Srdan Verstovsek, Marie Robin, Antonio Colecchia, Luigi Grazioli, Enrico Damiani, Domenico Russo, Jessica Brady, David Patch, Slawomir Blamek, Gandhi Laurent Damaj, Patrick Hayden, Donal P. McLornan, Ibrahim Yakoub-Agha
Summary: Splenomegaly is a common complication in myelofibrosis patients and can negatively impact outcomes of allogeneic hematopoietic cell transplantation (HCT). This Position Paper provides a shared position statement on the management of splenomegaly before HCT. The assessment, prevalence, and clinical significance of splenomegaly are discussed, along with the need for therapeutic intervention. Specific scenarios, such as splanchnic vein thrombosis and COVID-19, are also addressed.
LANCET HAEMATOLOGY
(2023)
Review
Hematology
Srdan Verstovsek
Summary: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by mutations (most frequently in JAK2, CALR, or MPL), burdensome symptoms, splenomegaly, cytopenia, and shortened life expectancy. In addition to other clinical manifestations, patients with MF often develop anemia, which can either be directly related to MF pathogenesis or a result of MF treatment with Janus kinase (JAK) inhibitors, such as ruxolitinib and fedratinib. This review provides detailed treatment and patient management approaches for both types of anemia presentations in MF and offers recommendations for the treatment of MF in the presence of anemia.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Lucia Masarova, Prithviraj Bose, Naveen Pemmaraju, Naval G. Daver, Koji Sasaki, Helen T. Chifotides, Lingsha Zhou, Hagop M. Kantarjian, Zeev Estrov, Srdan Verstovsek
Summary: This retrospective study evaluated the impact of different therapies on the survival of patients with myelofibrosis. The results showed that treatment with the JAK inhibitor ruxolitinib improved patient outcomes. Approximately 61% of patients initiated MF-directed therapy, with ruxolitinib being the most common choice. About 32% of patients required second-line therapy.
Article
Oncology
Srdan Verstovsek, Jean-Jacques Kiladjian, Alessandro M. M. Vannucchi, Ruben A. A. Mesa, Peg Squier, J. E. Hamer-Maansson, Claire Harrison
Summary: This study analyzed the impact of the timing of ruxolitinib treatment on clinical outcomes in patients with intermediate-2 and high-risk myelofibrosis. The results showed that patients who initiated treatment earlier had better outcomes in terms of thrombocytopenia and anemia, higher spleen volume response, and longer overall survival.
Review
Pharmacology & Pharmacy
Pankit Vachhani, Srdan Verstovsek, Prithviraj Bose
Summary: Cytopenic myelofibrosis is a subtype of myelofibrosis characterized by low blood counts, lower driver mutation allele burden, increased likelihood of occurring de novo, greater genomic complexity, worse survival, and higher rates of leukemic transformation. Several JAK inhibitors are available for clinical use, including pacritinib and momelotinib, which show promise in improving cytopenias. These newer JAK inhibitors may become the foundation for future combination therapies.
EXPERT OPINION ON PHARMACOTHERAPY
(2023)
Article
Oncology
John Mascarenhas, Marina Kremyanskaya, Andrea Patriarca, Francesca Palandri, Timothy Devos, Francesco Passamonti, Raajit K. Rampal, Adam J. Mead, Gabriella Hobbs, Joseph M. Scandura, Moshe Talpaz, Nikki Granacher, Tim C. P. Somervaille, Ronald Hoffman, Marielle J. Wondergem, Mohamed E. Salama, Gozde Colak, Jike Cui, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Srdan Verstovsek, Natalia Curto-Garcia, Claire Harrison, Vikas Gupta
Summary: In patients with myelofibrosis who are naive to JAKi treatment, the rational combination of the BET inhibitor pelabresib and ruxolitinib showed good tolerability and durable improvements in spleen and symptom burden.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Naveen Pemmaraju, Prithviraj Bose, Raajit Rampal, Aaron T. Gerds, Angela Fleischman, Srdan Verstovsek
Summary: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by splenomegaly, abnormal cytokine expression, cytopenias, and progressive bone marrow fibrosis. Ruxolitinib, an oral Janus kinase (JAK) 1 and JAK2 inhibitor, was the first approved agent for MF and has revolutionized the treatment approach. The understanding of MF has improved significantly due to targeted JAK1/JAK2 inhibition and extensive literature on ruxolitinib, leading to better management strategies and discussion on future treatment options.
LEUKEMIA & LYMPHOMA
(2023)
Article
Hematology
Ivan Krecak, Marko Skelin, Srdan Verstovsek
Summary: Interferons (IFNs) have been used for decades to treat polycythemia vera (PV). Single-arm clinical trials have shown high hematological and molecular response rates with IFNs, indicating potential disease-modifying activity. However, discontinuation rates of IFNs have been rather high due to frequent treatment-related side-effects.
EXPERT REVIEW OF HEMATOLOGY
(2023)
Review
Hematology
Ivan Krecak, Srdan Verstovsek, Marko Lucijanic
Summary: The exact prognostic role of cardiovascular risk factors in BCR-ABL1 negative MPN patients is unknown. Current treatment of CV risk factors in MPNs is not guided by the presence of these risk factors. Target levels for different metabolic deflections in MPNs have not been defined. This review discusses the important aspects of individual CV risk factors in MPNs, summarizes recent advances, and proposes future directions and research areas.
ANNALS OF HEMATOLOGY
(2023)
Review
Oncology
Srdan Verstovsek, Ruben A. Mesa, Robert A. Livingston, Wilson Hu, John Mascarenhas
Summary: Myelofibrosis is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Ruxolitinib, an oral JAK1/JAK2 inhibitor, has been approved for the treatment of intermediate or high-risk MF patients. It remains the standard of care for higher-risk MF, and dose optimization and management are crucial for maximizing its benefits.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Srdan Verstovsek, Ivan Krecak, Florian H. Heidel, Valerio De Stefano, Kenneth Bryan, Mike W. Zuurman, Michael Zaiac, Mara Morelli, Aoife Smyth, Santiago Redondo, Erwan Bigan, Michael Ruhl, Christoph Meier, Magali Beffy, Jean-Jacques Kiladjian
Summary: The PV-AIM study used machine learning to identify markers of thromboembolic events (TE) in patients with polycythemia vera (PV). The study found that lymphocyte percentage (LYP), neutrophil percentage (NEP), and red cell distribution width (RDW) are closely associated with TE risk, and can be used to identify high-risk patients.
Article
Hematology
Vikas Gupta, John Mascarenhas, Marina Kremyanskaya, Raajit K. Rampal, Moshe Talpaz, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Srdan Verstovsek, Gozde Colak, Debarshi Dey, Claire Harrison
Summary: A study suggests that pelabresib in combination with ruxolitinib may have higher efficacy in treating JAKi treatment-naive MF patients compared to JAKi monotherapy, with significant improvements in spleen volume reduction and total symptom scores.
Article
Hematology
Srdan Verstovsek, Ruben Mesa, Vikas Gupta, David Lavie, Viviane Dubruille, Nathalie Cambier, Uwe Platzbecker, Marek Hus, Blanca Xicoy, Stephen T. Oh, Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Aaron Gerds, Miklos Egyed, Jiri Mayer, Tomasz Sacha, Jun Kawashima, Marc Morris, Mei Huang, Claire Harrison
Summary: Momelotinib is a first-in-class inhibitor of Janus kinases 1 and 2, as well as activin A receptor type 1, and has shown efficacy in addressing the symptoms of myelofibrosis, such as splenomegaly, constitutional symptoms, and anemia. This long-term analysis of pooled data from three phase 3 studies demonstrated the safety and tolerability of momelotinib, with no evidence of long-term or cumulative toxicity. The most common adverse events were diarrhea and hematologic abnormalities, but they were generally manageable. This analysis provides valuable evidence supporting the use of momelotinib in the treatment of myelofibrosis.